Catalytic enantioselective construction of beta-quaternary carbons via a conjugate addition of cyanide to beta,beta-disubstituted alpha,beta-unsaturated carbonyl compounds

J Am Chem Soc. 2010 Jul 7;132(26):8862-3. doi: 10.1021/ja1035286.

Abstract

The first general catalytic enantioselective conjugate addition of cyanide to beta,beta-disubstituted alpha,beta-unsaturated ketones and N-acylpyrroles was developed using a strontium catalyst derived from Sr(O(i)Pr)(2) and new chiral ligand 5. The reaction exhibited excellent enantioselectivity and a wide substrate scope using 0.5-10 mol % catalyst. 1,4-Adducts containing beta-quaternary carbons were exclusively produced over 1,2-adducts. ESI-MS analysis of the strontium catalyst indicated that the active catalyst was a trimetallic Sr/5 = 3:5 complex. The exclusive 1,4-selectivity was partly due to the ability of the strontium complex to promote both a retro-cyanation reaction from the 1,2-adducts and highly enantioselective conjugate cyanation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbon / chemistry*
  • Catalysis
  • Ketones / chemistry*
  • Nitriles / chemistry*
  • Pyrroles / chemistry
  • Stereoisomerism
  • Substrate Specificity

Substances

  • Ketones
  • Nitriles
  • Pyrroles
  • Carbon